Five-year data from FAME (Fractional Flow Reserve vs. Angioplasty for Multivessel Evaluation) 2 show that patients with stable disease who undergo percutaneous coronary intervention (PCI) guided by fractional flow reserve (FFR) have significant fewer spontaneous myocardial infarctions than patients who receive optimal medical therapy. This is the first time a study of FFR-guided PCI has shown benefit in terms of a hard endpoint for PCI in stable disease.
At present, the use of PCI in stable disease—particularly in the wake of ORBITA—is controversial. According to Michael Haude (Medical Clinic I, Städtische Kliniken Neuss, Neuss, Germany), compared with optimal medical therapy, PCI with drug-eluting stents in patients with stable disease has shown “no or only a modest benefit in terms of survival or myocardial infarction” but has indicated symptom improvement and quality of life. However, he noted that while previous trials did not use the latest generation of drug-eluting stents, more recent trials have.
One such trial is FAME 2, which has already shown that FFR-guided PCI improves clinical outcomes with medical management in stable disease—according to data presented at the 2017 Transcatheter Cardiovascular Therapeutics (TCT) meeting (29 October–2 November, Denver, USA), FFR-guided PCI significantly reduced the risk of major adverse cardiac events at three years. Presenting the five-year data at EuroPCR (22 May—25 May, Paris, France), Panagiotis Xaplanteris (Cardiovascular Center Aalst, Onze-Lieve-Vrouw Clinic, Aalst, Belgium) reported that PCI continues to have a benefit over medical management in terms of the primary endpoint (all-cause death, myocardial infarction, and urgent revascularisation): 13.9% vs. 27% for medical management (p<0.001). He added that there were no significant differences in this endpoint between the PCI group and a registry group of patients who were excluded from the randomisation stage of the trial for having a stenosis with a FFR value of >0.80 (i.e. haemodynamically insignificant) and who received medical management only.
The main driver of the difference between the PCI group and the trial medical management group was urgent revascularisation: 6.3% for PCI vs. 21.1% for medical management (p<0.001). However, Xaplanteris commented: “What is new [with this FAME 2 analysis] is a very strong signal towards less myocardial infarction.” In a landmark analysis for myocardial infarction, PCI was associated with a significantly lower rate of spontaneous myocardial infarction compared with medical management (6.5% vs. 10.2%, respectively; p=0.04). There was no significant difference between groups in the rate of periprocedural myocardial infarction.
According to Xaplanteris, overall, PCI “offered sustained relief from angina”. “More than half of the medical therapy patients had crossed over to the PCI arm at five years, which most likely diluted the results, and decreased the number of hard-end points,” he observed.
Concluding, he said: “When FFR is >0.80, outcome is favourable with medical therapy [i.e. as in the registry group]. But what is new, is that when FFR is ≤0.80, PCI with drug-eluting stents provides sustained benefits in the need for urgent revascularisation, the rate of spontaneous myocardial infarction, symptomatic relief, and this is without late catch-up phenomenon.”
Commenting on the findings, Philip Urban (Cardiovascular Department, Hôpital de la Tour, Geneva, Switzerland) stated that the take-home message of the five-year findings were “If it ain’t broke, don’t fix it. If it is broke, don’t procrastinate!”
The study, which was simultaneously published in the New England Journal of Medicine, was just one of several presented at EuroPCR that showed a benefit for PCI guided by physiological assessment (instantaneous wave-free ratio, iFR, as well as FFR). The GZ FFR study, presented by Barry Hennigan (University of Glasgow, Glasgow, UK), indicated that PCI in stable disease patients with “grey zone” FFR values (0.75–0.80) reduced ischaemia (on stress MRI) by 50%, improved the Seattle Angina Questionnaire score in two out of five domains, and reduced angina frequency/improved quality of life compared with medical therapy; a pooled patient-level analysis of FAME 2, DANAMI-3-PRIMULTI, and COMPARE-ACUTE (presented by Frederik Zimmermann, Catharina Hospital Eindhoeven, Eindhoeven, The Netherlands) suggested a prognostic benefit of PCI in appropriately selected patients independent of symptoms; and data from SCAAR (presented by Elmir Omerovic, University of Gothenburg, Gothenburg, Sweden) showed a strong signal that FFR/iFR-guided PCI reduced overall mortality, restenosis, and stent thrombosis in patients with stable disease at 10 years.
Haude, on behalf of PCR and the European Association of Percutaneous Cardiovascular Interventions (EAPCI), commented that—together—the data presented at EuroPCR gave a “strong signal that physiology (FFR/iFR) guided PCI is superior over angio-guided PCI for mortality, restenosis and stent thrombosis up to 10 years”. He added that “the longer the observation period is, the more benefit is shown for PCI”
FAME-2 study investigator Bernard De Bruyne (Cardiovascular Center Aalst, Onze-Lieve-Vrouw Clinic, Aalst, Belgium) told Cardiovascular News: “The FAME 2 data put FFR central stage in the decision about PCI and indicate that when patients and lesions are properly selected, you had better have a good reason not to perform PCI—even in stable patients.”